Synthesis of 3H‐labelled levamisole

Publisher Website
Google Scholar
Abstract
Levamisole, the levo isomer of tetramisole, is a potent anthelmintic also showing immunotropic properties. Renewed interest in the latter domain necessitated the synthesis of specifically 3H‐labelled levamisole of high specific activity.Racemic 1‐(2‐bromophenyl)‐1,2‐ethane diamine dihydrochloride (V) was obtained via bromination of 1‐(2‐bromophenyl)ethanone (I), followed by reaction with 2,5‐pyrrolidinedione, Leuckart amination and hydrolysis. The racemate was then resolved by successive salt formation with (S)‐(‐) and (R)‐(+) tartaric acid. The liberated (S)‐(+)‐base of VI was dehalogerated with approximately 30 Ci of tritium gas and immediately ring‐closed with carbon disulfide to VIII. The HPLC‐purified material was finally cyclized with 1,2‐dibromo ethane to (S)‐(‐)‐2,3,5,6‐tetrahydro‐6‐[2‐T]phenyl‐imidazo‐(2,1‐b)‐thiazole IX and the isomerically ringclosed (S)‐2,3,5,6‐tetrahydro‐5‐[2‐T] phenyl‐imidazo‐(2,1‐b)‐thiazole X, of which levamisole IX was isolated via HPLC. The radiochemical yield over the cyclization steps was 28.2 %, the specific activity was 10.82 Ci/mmol, and the product was 99.9 % HPLC pure.